ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1702G>A (p.Gly568Ser)

gnomAD frequency: 0.00007  dbSNP: rs140464432
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000119225 SCV000153969 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 568 of the RET protein (p.Gly568Ser). This variant is present in population databases (rs140464432, gnomAD 0.03%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 30217742). ClinVar contains an entry for this variant (Variation ID: 132762). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Possibly Damaging". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga) RCV000355156 SCV000339854 uncertain significance not provided 2016-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564831 SCV000674795 likely benign Hereditary cancer-predisposing syndrome 2020-10-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000662493 SCV000785005 uncertain significance Multiple endocrine neoplasia type 2A 2017-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477302 SCV000896057 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2024-04-23 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000564831 SCV002529943 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-18 criteria provided, single submitter curation
GeneDx RCV000355156 SCV002586596 uncertain significance not provided 2024-04-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Reported in an individual with vesicoureteral reflux (PMID: 36549658); This variant is associated with the following publications: (PMID: 36705391, 14633923, 36549658)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000355156 SCV005623071 uncertain significance not provided 2024-03-27 criteria provided, single submitter clinical testing

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